Transdermal patches are known and used since the years 1979 to administrate to patients, by means of diffusion through the dermis, a certain dose of active ingredient into the body via the blood or the lymph thanks to body heat and to the solubility of the active ingredient. One of the advantages of the transdermal administration of a drug with respect to the other oral, topical or inhalation, etc., types of administration is the fact that it allows a slow release of the drug. However, the skin, which forms an efficient barrier, is a limitation for this method of administration. Nevertheless, a wide variety of active ingredients can be delivered transdermally. Another advantage of this method of administration lies in the fact that it takes place automatically, without any intervention of the patient and without any risk of omission or overdosage. A further advantage is the significant reduction of the adverse effects linked with the other methods of administration of drugs, orally, by inhalation, etc. And another advantage is the reduction of the active ingredients required to produce the same effects, as they are diffused directly in the body via the blood, the lymph or the tissues, without having to pass through other organs, in particular the digestive tract.
The commercially available transdermal patches generally comprise a package that protects the patch during storage and that is removed prior to use, a patch comprising a side intended to be applied against the skin and which contains a dose of active ingredient or drug in solution to pass through the skin, and a watertight back that protects the patch against the environment, an adhesive used both to hold the patch components together and to fasten the patch onto the skin, and a membrane laid over the patch side in contact with the skin to control the release of the drug.
The market is dominated by the so-called passive transdermal patches, which means that these diffuse continuously a determined quantity of active ingredients for a determined duration from the moment the patch is applied on the skin. This type of transdermal patches is indicated to treat in particular pain, tobacco dependence and the disorders related to menopause in women.
Other so-called active transdermal patches have been developed to control the diffusion of the active ingredients through the skin using various control means such as heat, micro-currents, light, micro-injection. Likewise, most of the transdermal patches are designed to diffuse one single active ingredient. In very specific cases, such as menopause treatment, certain transdermal patches diffuse a combination of two active ingredients. Furthermore, in all known transdermal patches, the active ingredient is stored directly in the substrate, which is in constant contact with the skin and which is a significant cause of allergy, independently of the active ingredient itself. In addition, the active ingredient can migrate or degrade when in contact with the skin.
One constantly tries to reduce the size of the transdermal patch, improve its performances in terms of therapeutic efficacy and personalize it to adapt the dosage to the patient in function of the disease(s) to be treated.
One of the solutions is in particular described in patent U.S. Pat. No. 7,991,464, which offers a transderrnal patch wherein the active ingredient is bonded to the substrate of the transdermal patch by means of a photolabile bond sensitive to the action of an evanescent field produced by a light pulse in the ultraviolet range through the polymer substrate that forms a light guide. The light pulse that releases the active ingredient is generated by a light-emitting diode (LED) operated by an electronic circuit and arranged opposite to the edge of the substrate in order to diffuse the evanescent field in the thickness of said substrate. A prior software-performed reaction kinetics study allows determining the illumination time required to release a determined quantity of active ingredient. This data is processed by the microprocessor integrated in the electronic circuit. This technology allows personalizing the dosage of said patch and correcting the dosage if necessary.
However, this technology is limited to the delivery of one single active ingredient. It is also limited in terms of quantity of stored active ingredient, as the limit is imposed by the two-dimensional surface of the transdermal patch. Moreover, not all molecules of the active ingredients liable to be used are compatible with the photolabile ligands, which considerably restricts the therapeutic applications of such transdermal patch.
Publication US 2006/0024358 describes a transdermal device comprising several tanks with the purpose of releasing various active ingredients in a way that can be controlled and modified. These tanks are closed by a lid arranged to disintegrate electrically or thermally and release the active ingredient towards the skin of the patient through a matrix serving as a vehicle and a permeable adhesive membrane. Nevertheless, these tanks are arranged on a same plane, thus limiting the quantity of active ingredient that can be stored.
Publication WO 2004/060447 describes a transdermal device wherein the active ingredients are encapsulated in microparticles or nanoparticles dispersed in a monolithic matrix such as a hydrogel. The active ingredients are released by causing the envelope of the microparticles to break using ultrasound and/or heat. However, this device does not comprise several tanks for storing various active ingredients.
Publication US 2006/0173514 relates to an electrotherapy wound treatment. The dressing comprises in particular a matrix made out of a hydrogel or a foam and a light source coupled with a battery. It is applied on the wound after having applied a photosensitive active ingredient on said wound. It therefore does not contain active ingredients stored in tanks and diffused in a controlled way.
Publication U.S. Pat. No. 5,464,387 describes an iontophoresis transdermal device using two electrodes coupled each to a tank of active ingredients and connected serially with an energy source. It furthermore comprises a passive tank in the form of a hydrogel arranged to release continuously an active ingredient by means of simple diffusion. This device does not comprise tanks allowing storing a large quantity of active ingredients.
Therefore the existing solutions are not satisfactory.